The present invention relates generally to microneedle arrays and is particularly directed to a method for manufacturing microneedle structures using soft lithography and photolithography. The invention is specifically disclosed as a method of manufacturing microneedles by creating micromold structures made of a photoresist material or PDMS, and in some cases using a sacrificial layer for ease of separation from a substrate layer.
Topical delivery of drugs is a very useful method for achieving systemic or localized pharmacological effects, although there is a main challenge involved in providing sufficient drug penetration across the skin. Skin consists of multiple layers, in which the stratum corneum layer is the outermost layer, then a viable epidermal layer, and finally a dermal tissue layer. The thin layer of stratum corneum represents a major barrier for chemical penetration through the skin. The stratum corneum is responsible for 50%-90% of the skin barrier property, depending upon the drug material""s water solubility and molecular weight.
An alternative to the use of hypodermic needles for drug delivery by injection is disclosed in U.S. Pat. No. 3,964,482 (by Gerstel), in which an array of either solid or hollow microneedles is used to penetrate through the stratum corneum and into the epidermal layer. Fluid is dispensed either through the hollow microneedles or through permeable solid projections, or perhaps around non-permeable solid projections that are surrounded by a permeable material or an aperture. A membrane material is used to control the rate of drug release, and the drug transfer mechanism is absorption.
Other types of microneedle structures are disclosed in WO 98/00193 (by Altea Technologies, Inc.), and in WO 97/48440, WO 97/48441, and WO 97/48442 (by Alza Corp.). In addition, WO 96/37256 discloses another type of microblade structure.
The use of microneedles has one great advantage in that intracutaneous drug delivery or drug sampling can be accomplished without pain and without bleeding. As used herein, the term xe2x80x9cmicroneedlesxe2x80x9d refers to a plurality of elongated structures that are sufficiently long to penetrate through the stratum corneum skin layer and into the epidermal layer. In general, the microneedles are not to be so long as to penetrate into the dermal layer, although there are circumstances where that would be desirable. Since microneedles are relatively difficult to manufacture, it would be an advantage to provide methodologies for constructing microneedles that are made from various types of micromolds that can be manufactured relatively quickly. The use of metallic molds or semiconductor molds is possible, but such structures usually take a relatively long period of time for construction. On the other hand, if the molds are made of a polymer or other type of plastic (or other moldable) material, then such mold structures can be made relatively quickly and with much less expense.
Accordingly, it is an advantage of the present invention to provide a method for fabricating microneedles using photolithography and soft lithography techniques, which allow for quick manufacturing of both micromolds and usable microneedle structures.
It is another advantage of the present invention to provide a method for fabricating microneedles in which a photoresist material is applied in a single layer, or in multiple layers, and patterned via photolithography, thereby either creating a microneedle structure that can be directly used, or creating micromold structure that can be used with moldable material such as polymers to manufacture the microneedle structures.
It is a further advantage of the present invention to provide a method for fabricating microneedles in which soft lithography is used to create microneedle structures that can be directly used, or to create micromold structures that can be used with moldable material such as polymers to manufacture the microneedle structures, in which a moldable material has its shape formed, at least in part, by another relatively xe2x80x9csoftxe2x80x9d materialxe2x80x94e.g., something other than a metal.
It is still another advantage of the present invention to provide a method for fabricating microneedles in which soft lithography is used to create microneedle structures that can be used to create flexible micromold structures that can be used with moldable material such as polymers to manufacture the microneedle structures, in which the resulting microneedle array is either concave or convex in overall shape.
It is yet a further advantage of the present invention to provide a method for fabricating microneedles in which photolithography and/or soft lithography is used to create micromold structures, and in which a sacrificial layer of material is dissolved or decomposed to separate the micromold structures from a substrate.
It is still a further advantage of the present invention to provide a method for fabricating microneedles in which photolithography and/or soft lithography is used to create microneedle structures, and further coating a surface of the microneedle structures using a vapor deposition process, and/or another coating process such as: electroplating, electrodeposition, electroless plating, sputtering, or plasma deposition.
It is yet another advantage of the present invention to provide a method for fabricating microneedles in which photolithography and/or soft lithography is used to create master structures, and further using a microembossing or molding process to manufacture microneedle structures.
It is still another advantage of the present invention to provide a method for fabricating microneedles in which photolithography and/or soft lithography is used to create microneedle structures, and further creating electrodes on the microneedle structures, either in xe2x80x9cbandsxe2x80x9d of electrically conductive material that each encompass multiple microneedles, or in individual small electrically conductive structures that run inside a single hollow microneedle.
It is a further advantage of the present invention to provide a method for fabricating microneedles in which photolithography and/or soft lithography is used to create microneedle structures, in which the tips of the microneedles are either hardened or made more flexible, or in which the base (or substrate) of the microneedle array is made more flexible, or in which the microneedles break away from the base (substrate) of the array after application to skin, thereby leaving behind hollow microtubes that protrude through the stratum corneum.
Additional advantages and other novel features of the invention will be set forth in part in the description that follows and in part will become apparent to those skilled in the art upon examination of the following or may be learned with the practice of the invention.
To achieve the foregoing and other advantages, and in accordance with one aspect of the present invention, a method for fabricating microneedles is provided including steps of: (a) providing a substrate that includes multiple microstructures; (b) coating the substrate with a layer of a first moldable material that takes the negative form of the microstructures, and hardening the first moldable material; (c) separating the hardened first moldable material from the substrate, and creating a micromold from the hardened first moldable material containing the microstructures; and (d) applying a second moldable material onto the micromold, allowing the second moldable material to harden using a soft lithography procedure, then separating the hardened second moldable material from the micromold, thereby creating a microneedle structure from the hardened second moldable material having the three-dimensional negative form of the microstructures of the patterned micromold.
In accordance with another aspect of the present invention, a method for fabricating microneedles is provided including steps of: (a) providing a substrate material; (b) coating the substrate material with at least one layer of a photoresist material, and patterning the photoresist material with multiple microstructures by use of a photolithography procedure; and (c) separating the patterned photoresist material from the substrate material, thereby creating a microneedle structure from the patterned photoresist material containing the microstructures.
In accordance with a further aspect of the present invention, a method for fabricating microneedles is provided including steps of: (a) providing a substrate material; (b) coating the substrate material with at least one layer of a photoresist material, and patterning the photoresist material with multiple microstructures by use of a photolithography procedure; (c) coating the patterned photoresist material with a layer of moldable material that takes the negative form of the microstructures, and allowing the moldable material to harden using a soft lithography procedure, then separating the hardened moldable material from both the patterned photoresist material and the substrate material; and (d) coating at least one surface of the separated hardened moldable material by use of a vapor deposition procedure.
In accordance with yet a further aspect of the present invention, a method for fabricating microneedles is provided including steps of: (a) providing a substrate material; (b) coating the substrate material with at least one layer of a photoresist material, and patterning the photoresist material with multiple microstructures by use of a photolithography procedure; (c) applying a first moldable material onto the patterned photoresist material/substrate and allowing the first moldable material to harden using a soft lithography procedure, then separating the hardened first moldable material from the patterned photoresist material/substrate to create a microstructure; and (d) molding or embossing a second moldable material onto the microstructure, and after hardening of the second moldable material, separating the hardened second moldable material from the microstructure, thereby creating a microneedle structure from the hardened second moldable material having the three-dimensional negative form of the microstructure.
In accordance with still a further aspect of the present invention, a method for fabricating microneedles is provided including steps of: (a) providing a substrate material; (b) coating the substrate material with at least one layer of a photoresist material, and patterning the photoresist material with multiple microstructures by use of a photolithography procedure, such that the patterned photoresist material comprises the microstructures; (c) coating the substrate with a layer of moldable material that takes the negative form of the microstructures, and hardening the moldable material by a soft lithography procedure; (d) separating the hardened moldable material from the substrate, thereby creating a mask; (e) providing a microneedle array structure having multiple individual protrusions extending from a base; and (f) positioning the mask proximal to the microneedle array structure and applying an electrically conductive substance through the mask onto a surface of the microneedle array structure, thereby creating at least one pattern of electrically conductive pathways on the surface.
In accordance with still another aspect of the present invention, a microneedle structure is provided which comprises a longitudinal element having a first end and a second end, in which the longitudinal element has a side wall extending between the first end and the second end; and the side wall also has at least one external channel running between substantially the first end and the second end.
Still other advantages of the present invention will become apparent to those skilled in this art from the following description and drawings wherein there is described and shown a preferred embodiment of this invention in one of the best modes contemplated for carrying out the invention. As will be realized, the invention is capable of other different embodiments, and its several details are capable of modification in various, obvious aspects all without departing from the invention. Accordingly, the drawings and descriptions will be regarded as illustrative in nature and not as restrictive.